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Engineered peptide-drug conjugate provides sustained protection of retinal ganglion cells with topical administration in rats.

Authors :
Hsueh, Henry T.
Chou, Renee Ti
Rai, Usha
Kolodziejski, Patricia
Liyanage, Wathsala
Pejavar, Jahnavi
Mozzer, Ann
Davison, Charlotte
Appell, Matthew B.
Kim, Yoo Chun
Leo, Kirby T.
Kwon, HyeYoung
Sista, Maanasa
Anders, Nicole M.
Hemingway, Avelina
Rompicharla, Sri Vishnu Kiran
Pitha, Ian
Zack, Donald J.
Hanes, Justin
Cummings, Michael P.
Source :
Journal of Controlled Release. Oct2023, Vol. 362, p371-380. 10p.
Publication Year :
2023

Abstract

Effective eye drop delivery systems for treating diseases of the posterior segment have yet to be clinically validated. Further, adherence to eye drop regimens is often problematic due to the difficulty and inconvenience of repetitive dosing. Here, we describe a strategy for topically dosing a peptide-drug conjugate to achieve effective and sustained therapeutic sunitinib concentrations to protect retinal ganglion cells (RGCs) in a rat model of optic nerve injury. We combined two promising delivery technologies, namely, a hypotonic gel-forming eye drop delivery system, and an engineered melanin binding and cell-penetrating peptide that sustains intraocular drug residence time. We found that once daily topical dosing of HR97-SunitiGel provided up to 2 weeks of neuroprotection after the last dose, effectively doubling the therapeutic window observed with SunitiGel. For chronic ocular diseases affecting the posterior segment, the convenience of an eye drop combined with intermittent dosing frequency could result in greater patient adherence, and thus, improved disease management. [Display omitted] • A hypotonic gel-forming eye drop was used to increase drug delivery to posterior segment to protect retinal ganglion cells. • Conjugation of sunitinib to the engineered melanin binding and cell-penetrating peptide increased intraocular residence time. • The peptide-drug conjugate in the hypotonic gel-forming eye drop (HR97-SunitiGel) provided sustained ocular drug delivery. • HR97-SunitiGel has potential for improving disease management in chronic ocular diseases affecting the posterior segment. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01683659
Volume :
362
Database :
Academic Search Index
Journal :
Journal of Controlled Release
Publication Type :
Academic Journal
Accession number :
172871247
Full Text :
https://doi.org/10.1016/j.jconrel.2023.08.058